Antimalarials

Question 1

Artemisinin Drugs - names and stage and which they are active

Answer 1

Artemether
ACT with Lumefantrine
Blood stage

Question 2

Quinolones and related compounds - names and active stage

Answer 2

Blood stage -
Quinine sulfate
Chloroquine Phosphate

Blood and Primary Liver Stages
Primaquine

Question 3

Adjunctive antibiotics with Quinolones

Answer 3

Doxycycline
Clindamycin
Atovaquone-Proguanil - primary liver and blood stages

Question 4

Why is more than one drug used in malaria treatment

Answer 4

The parasite is at different life cycle stages in the patient. No one drug is effective against all stages.

Question 5

Artemisinin Mechanism of Action

Answer 5

Not really known - it MAY create a peroxide “bridge” in proteins that is rdeuced by heme, creating toxic metabolites that kill the parasite, but no one really knows.

Question 6

Artemisinin ADME

Answer 6

PO/IV
Rapd absorbtion/metabolism
Protein bound distribution
Hepatic metabolism CYP34A and 2B6 inducer
Short T 1/2 - pair with other drugs (artemether - Lumefanrtine) for ACT - 1st line treatment

Question 7

Artemisin Adverse effects

Answer 7

Generally well tolerated, not recommended for kids under 5kg or 1st trimester.

Decreased RBC’s, neutrophils, increased LFT’s.

Question 8

Quinolone mechanism of action

Answer 8

Interferes with heme digestion

Question 9

Quinolone ADME

Answer 9

PO, IV, IM
Readily absorbed T1/2 11hrs
Good tissue distribution, including fetus (safe)
Protein Bound
Hepatic Metabolism CYP3A4
Renal Excretion

Question 10

Quinolone resistance mechanism and location

Answer 10

Pfmdr1 gene mutation - Southeast Asia, South Africa

Question 11

Quinine adverse effects

Answer 11

Generally well tolerated, but overdose can be fatal (2-8g)
Cinchonism - Tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, flushing.

Hepatic abnormalities/hemolysis/hypotension/ cardio toxicity

Question 12

Quinine Contraindications

Answer 12

Hypersensitivity
Hemolysis
Tinnitus/optic neuritis
Caution in cardiac dysrythmia
POTENTIALLY safe in pregnancy

Question 13

Quinine DDI’s

Answer 13

Aluminum-containing antacids delay absorption.
Increased warfarin and digoxin levels
decrease dose with renal insufficiency

Question 14

Adjunctive Therapies for use with Qunine/Quinidine

Answer 14

Doxycycline, Clindamycin - inhibit protein translation - death of progeny protozoa.

Question 15

Chloroquine

Answer 15

Plasma concentration determined by distribution/elimination rate - parentral can result in a potentially lethal concentration- requires a loading dose.

Question 16

Chloroquine Resistance

Answer 16

pfcrt mutation, drug efflux

Question 17

Chloroquine Toxicity

Answer 17

Narrow safety margin for dosing
Acute toxicity - CV and CNS
>5g parentral usually fatal
Pruritis in patients of African descent.

Question 18

Primaquine ADME

Answer 18

PO
excellent adsorption
Large Vd
Protein Bound
Rapid CYP1A2 metabolism
Renal excretion

Question 19

Primaquine Contraindications

Answer 19

Hemolysis in G6PD deficiency! Screen First!

CI in pregnancy

Question 20

Atovaquone mechanism

Answer 20

Inhibits parasite mitochondrial electron transport chain.

Question 21

Atovaquone Use

Answer 21

chemoprophylaxis, uncomplicated P. Falcipicarum.

Question 22

Atovaquone ADME

Answer 22

PO 
Slow erratic absorption
Protein bound distribution
No significant Metabolism
Biliary Excretion

Question 23

Atovaquone Resistance

Answer 23

Cytochrome B mutations

Question 24

Atovaquone DDI’s

Answer 24

Rifampin/Tetracycline decrease plasma levels

Question 25

Proguanil mechanism

Answer 25

Inhibits dihydrofolate reductase, enhances atovaquone effects. Safe in conjunction with atovaquone.